Volume 79 (2013), No. 5/2013(May)
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In-Depth Review
ESA therapy – the quest continues: anemia treatment following recent national and international recommendations 2011 and 2012
Patrick Biggar and Markus Ketteler
Page No. 335
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (335-350)
ESA therapy – the quest continues: anemia treatment following recent national and international recommendations 2011 and 2012
Patrick Biggar and Markus Ketteler
Nephrology Department, Klinikum Coburg, Coburg, Germany
The development of ESA (Erythropoiesis Stimulating Agents) revolutionized the treatment of renal anemia. However, the initial euphoria has abated and, in the last few years, studies have shown that ESAs should not be administered without caution as the rate of cardiovascular events and possibly tumor related deaths may increase with over-augmented hemoglobin levels. Renal anemia therapy is discussed against the background of recent decisions to lower the recommended hemoglobin target ranges in chronic kidney disease (CKD) patients on ESAs, thus, necessitating a redefinition of treatment quality criteria and exposing areas requiring further research.Correspondence to:
Dr. Patrick H. Biggar
Klinikum Coburg, Nephrology Department
Ketschendorfer Straße 33
96450 Coburg, Germany
Email: [email protected]
Original
Impact of statins on nephrolithiasis in hyperlipidemic patients: a 10-year review of an equal access health care system
Roger L. Sur, James H. Masterson, Kerrin L. Palazzi, James O. L’Esperance, Brian K. Auge, David C. Chang and Marshall L. Stoller
Page No. 351
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (351-355)
Impact of statins on nephrolithiasis in hyperlipidemic patients: a 10-year review of an equal access health care system
Roger L. Sur1,2,3,4, James H. Masterson4, Kerrin L. Palazzi1, James O. L’Esperance3,4, Brian K. Auge3,4, David C. Chang1 and Marshall L. Stoller5
1Department of Surgery, UC San Diego Health System, 2Department of Surgery, VA San Diego Healthcare System, San Diego, CA, 3Uniformed Services University of the Health Sciences, Bethesda, MD, 4Naval Medical Center San Diego, San Diego, CA, and 5Department of Urology, UC San Francisco, San Francisco, CA, USA
Aim: To investigate the impact of statin medications on urinary stone formation in hyperlipidemic patients. Material and methods: We searched outpatient military electronic health records from the Southwestern United States to identify adult patients with hyperlipidemia and urolithiasis. Military facilities serve active duty members, retirees, and their immediate family members. We created two predictor variables – with and without statin. The outcome variable was a diagnosis of urolithiasis. Results: The inception cohort included 57,232 subjects with hyperlipidemia and 1,904 subjects with nephrolithiasis. Patients taking statin medications had significantly less stone formation compared to patients not taking statin medications (3.1% vs. 3.7%, univariate OR = 0.83, 95% CI 0.76 – 0.91, p < 0.001). Statins patients were significantly older (59 vs. 45 years, p < 0.001), more likely to be female (38% vs. 34%, p < 0.001) and have co-morbidities (obesity, hypertension, diabetes, heart disease; all p < 0.001). Multivariate analysis indicated that statin medications had a protective effect against stone formation (OR = 0.51, 95% CI 0.46 – 0.57, p < 0.001), after adjusting for age, sex, and comorbidities. The risk of nephrolithiasis was not only additive for diabetes mellitus, hypertension, and obesity; more importantly it was attenuated with addition of statin use. Conclusion: Statin medications are associated with reduced risk of urinary stones. This is the first study to demonstrate the impact of statins on nephrolithiasis. Further prospective studies are necessary to validate these findings that treatment of hyperlipidemia reduces stone risk formation.Correspondence to:
Roger L. Sur, MD
UC San Diego Medical Center
Division of Urology
200 W Arbor Dr. #8897
San Diego, CA 92103-8897, USA
Email: [email protected]
Original
Elevated serum Cystatin C at continuous renal replacement therapy initiation predicts lack of renal recovery
Zhongheng Zhang, Hongying Ni, Baolong Lu and Ni Jin
Page No. 356
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (356-361)
Elevated serum Cystatin C at continuous renal replacement therapy initiation predicts lack of renal recovery
Zhongheng Zhang, Hongying Ni, Baolong Lu and Ni Jin
Department of Critical Care Medicine, Jinhua Municipal Central Hospital, Zhejiang, China
Background and objective: Serum Cystatin C (sCyC) has been associated with renal function, and it rises earlier than creatinine after renal injury. However, its role in predicting renal recovery in critically ill patients after continuous renal eplacement therapy (CRRT) remains untested. The study aimed to investigate the association of CyC with renal recovery in critically ill patients requiring CRRT. Methods: Medical charts of AKI patients that had been admitted to a tertiary 15-bed intensive care unit from January 2006 to January 2008 were reviewed. Renal recovery was defined as the return to pre-morbid renal function (sCr < 1.5 × premorbid sCr), or as an improvement in RIFLE classification. Univariate analyses with t test or Wilcoxon Rank-Sum test were performed to screen predictors of renal recovery, and multivariate Logistic regression analysis was performed to identify independent predictors of renal outcome. Diagnostic performance of sCyC was assessed. Results: Younger age and lower sCyC values were independent predictors of renal recovery (OR: 0.96 and 0.58, respectively); the area under the receiver operating characteristic curve (AU-ROC) of sCyC in predicting renal recovery was 0.66 (95% CI: 0.51 – 0.81), with the sensitivity and specificity of 57.69% and 86.79% at the cutoff of 3.13 mg/l. Conclusion: Elevated cystatin C at CRRT initiation predicts lack of renal recovery, but its diagnostic performance is suboptimal. Our study was limited by the small sample size and the lack of strict protocols on the initiation and cessation CRRT.Correspondence to:
Zhongheng Zhang
351#, Mingyue Road
Jinhua, Zhejiang province, 321000, China
Email: [email protected]
Original
Impact of cystatin C elevation and albuminuria on probability of adverse outcomes in HIV-infected men receiving HAART
Naoki Yanagisawa, Minoru Ando, Ken Tsuchiya and Kosaku Nitta
Page No. 362
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (362-369)
Impact of cystatin C elevation and albuminuria on probability of adverse outcomes in HIV-infected men receiving HAART
Naoki Yanagisawa, Minoru Ando, Ken Tsuchiya and Kosaku Nitta
Department IV of Internal Medicine, Tokyo Women’s Medical University, Kawada-cho, Shinjuku-ku, Tokyo, Japan
Background: Highly active antiretroviral therapy (HAART) has contributed to the longevity of human immunodeficiency virus (HIV)-infected patients; however, improved survival has been accompanied by an increase in the prevalence of kidney disease. Kidney disease may be partly responsible for higher morbidity in HIV-infected patients than in HIV-uninfected subjects. Methods: A total of 515 well-controlled HIVinfected men on HAART was enrolled in a 3-year prospective cohort study. The incidence of cancer and CVD was investigated over time. The impact of cystatin C elevation and albuminuria at baseline on the incidence of each disease was examined. Albuminuria was estimated by determining the albuminto-creatinine ratio (ACR). The cumulative incidence of cancer and CVD was analyzed using the Kaplan-Meier method, stratified by the presence and absence of elevated cystatin C and albuminuria biomarkers. Cox proportional hazards analysis was used to calculate the hazards ratio (HR) and 95% incidence interval (CI) of each biomarker, adjusted for known risk factors. Results: All participants completed the 3-year follow-up study. During the follow-up period, cancers and CVD developed in 13 (2.5%) and 14 (2.7%) participants, respectively. The Kaplan-Meier estimates were significantly increased for cancer incidence in patients with cystatin C elevation and for CVD in those with albuminuria. The HR (95% CI) of cystatin C elevation for occurrence of cancer was 6.09 (1.30 – 24.6) and the HR (95% CI) of ACR ≥ 20 mg/g for CVD was 8.97 (2.20 – 60.8). Conclusions: Cystatin C elevation and/or albuminuria at baseline in HIV-infected men undergoing HAART may be associated with poor prognosis.Correspondence to:
Minoru Ando, MD
Department of Nephrology
Tokyo Metropolitan Komagome Hospital
3-18-22, Honkomagome, Bunkyo-Ku
Tokyo, 113-0021, Japan
Email: [email protected]
Original
High-dose intravenous epoetin does not increase blood pressure in critically ill patients with acute kidney injury
Azrina M. Ralib, John W. Pickering, Tamas Major, Suetonia C. Palmer, Geoffrey M. Shaw, David A. Goodkin and Zoltán H. Endre
Page No. 370
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (370-379)
High-dose intravenous epoetin does not increase blood pressure in critically ill patients with acute kidney injury
Azrina M. Ralib1, John W. Pickering1, Tamas Major1, Suetonia C. Palmer1, Geoffrey M. Shaw1, David A. Goodkin2 and Zoltán H. Endre1,3
1Christchurch Kidney Research Group, Department of Medicine, University of Otago, Christchurch, New Zealand, 2Goodkin Biopharma Consulting, LLC, Bellevue, Washington, USA, and 3Department of Nephrology, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
Aims: Treatment of renal anemia with erythropoietic stimulating agents sometimes increases blood pressure. It is uncertain whether this is due to direct vasoconstriction and/or increased red blood cell mass. Materials and methods: We conducted a post-hoc analysis of 160 critically ill patients in the EARLYARF trial with elevated urinary γ-glutamyltranspeptidase and alkaline phosphatase, indicating acute kidney injury. Patients received 2 doses of intravenous (i.v.) epoetin (500 U/kg), 24 hours apart, or placebo, in a randomized, double-blind study design. Hourly intra-arterial mean arterial pressure (MAP), and norepinephrine equivalent dose (NED: determined using equipotency conversion factors for doses of epinephrine, vasopressin, phenlyephrine, or dopamine) were extracted from clinical records. The differences between baseline and maximum MAP and NED (ΔMAP and ΔNED) over 4, 24, 72-hour, and 30-day periods following study drug administration were compared between groups. Results: At baseline, MAP was 78 ± 14 mmHg in the epoetin group and 81 ± 15 mmHg in the placebo group (p = 0.22). There were no differences between groups in ΔMAP (6 ± 14 versus 7 ± 14 mmHg; p = 0.53), in ΔNED, or in ΔMAP adjusted for ΔNED at 4 hours, or at any time points. A subgroup analysis of only those patients not requiring vasopressor support (n = 71) also showed no differences between epoetin and placebo for all outcomes. Conclusion: We concluded that intravenous high dose epoetin does not acutely increase blood pressure, suggesting no acute vasoconstrictor effect in this setting.Correspondence to:
Professor Zoltán Endre
Department of Nephrology
Prince of Wales Hospital
High Street, Randwick, Sydney NSW2031, Australia
Email: [email protected]
Original
Bone mineral density 5 years after parathyroidectomy in hemodialysis patients with secondary hyperparathyroidism
Masayuki Yamanouchi, Yoshifumi Ubara, Noriko Hayami, Tatsuya Suwabe, Rikako Hiramatsu, Keiichi Sumida, Eiko Hasegawa, Junichi Hoshino, Naoki Sawa, Kiho Tanaka, Yuji Marui, Michio Nakamura, Shinji Tomikawa and Kennmei Takaichi
Page No. 380
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (380-386)
Bone mineral density 5 years after parathyroidectomy in hemodialysis patients with secondary hyperparathyroidism
Masayuki Yamanouchi, Yoshifumi Ubara, Noriko Hayami, Tatsuya Suwabe, Rikako Hiramatsu, Keiichi Sumida, Eiko Hasegawa, Junichi Hoshino, Naoki Sawa, Kiho Tanaka, Yuji Marui, Michio Nakamura, Shinji Tomikawa and Kennmei Takaichi
Nephrology Center, Toranomon Hospital, Tokyo, Japan
Background: Whether bone mineral density (BMD) is improved at 5 years after parathyroidectomy (PTx) for secondary hyperparathyroidism (SHPT) remains unknown. Objective: To investigate BMD after PTx by dual energy X-ray absorptiometry (DXA). Methods: BMD was measured at the distal 1/3 of the radius (nonshunt side) and at the lumbar supine (L2-L4, lateral view) before and 5 years after PTx in 35 hemodialysis patients who had undergone surgery from April 1994 to May 2004. The data were analyzed retrospectively. Results: Intact PTH decreased significantly from 1,100 ± 530 (range: 446 – 2,300) pg/ ml before PTx to 75 ± 68 (2 – 251) pg/ml at 5 years after PTx (p < 0.01). Before PTx, the radial BMD and lumbar BMD were both decreased –3.3 ± 1.9 SD and –1.3 ± 2.4 SD compared with the corresponding normal mean T-score, respectively. Radial BMD increased significantly from 0.522 ± 0.113 g/cm2 before PTx to 0.545 ± 0.114 g/cm2 (p = 0.01) at 5 years after PTx, while the Tscore improved to –2.8 ± 2.0 SD. In contrast, lumbar BMD showed no significant change between before (0.734 ± 0.202 g/cm2) and 5 years after PTx (0.746 ± 0.199 g/cm2), and neither did the T-score (–1.1 ± 2.3 SD). None of the patients suffered any fractures during follow up. Conclusion: These findings indicate that maintaining iPTH at < 300 pg/ml for 5 years after PTx results in an increase of radial BMD in SHPT patients with preoperative BMD levels in the osteoporosis range (below –2.5 SD) according to the WHO, as well as stabilizing lumbar BMD.Correspondence to:
Masayuki Yamanouchi, MD
Nephrology Center, Toranomon Hospital
2-2-2, Toranomon, Minatoku, Tokyo, 105-8470, Japan
Email: [email protected]
Original
Reduction of morbidity related to emergency access to dialysis with very low protein diet supplemented with ketoacids (VLPD+KA)
Marta Duenhas, Elsa Gonçalves, Mônica Dias, Graziela Leme and Sandra Laranja
Page No. 387
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (387-393)
Reduction of morbidity related to emergency access to dialysis with very low protein diet supplemented with ketoacids (VLPD+KA)
Marta Duenhas, Elsa Gonçalves, Mônica Dias, Graziela Leme and Sandra Laranja
Nephrology Division, Hospital do Servidor Público Estadual, São Paulo, Brazil
Objective: To delay the beginning of the renal replacement therapy (RRT) until the AV fistula is either made and mature or the training for peritoneal dialysis (PD) is given. Design: Prospective study. Setting: Nephrology’s Ambulatory, Hospital Servidor Público Estadual. Patients: 21 patients with chronic kidney disease (CKD) have been followed. Methods: For a period of 30 days, a VLPD+KA would be prescribed until the AV fistula was made or the PD training was given The patients were evaluated prior to the beginning of the VLPD+KA, on the 15th and the 30th day, and at the end of the study, with physical and nutritional evaluation, laboratory tests and 24-hour excretion of urinary urea and urinary protein, creatinine and urea residual clearance. Results: 47.6% (10/21) of the patients have initiated HD with matured and suitable AV fistula made in 30 days; 33.3% (7/21) of the patients have been unfit to initiate RRT, even though with sufficient time for the creation of the AV fistula or the training for PD due to AV fistula thrombosis; 14.3% (3/21) of the patients have remained in the study with no need for dialysis, and 4.8% (1/21) have been excluded on the grounds of not having adhered to the VLPD+KA. The anthropometric parameters and the energyintake have not differed from one period to the other. Conclusion: The VLPD+KA is safe to maintain the nutritional status of patients of CKD until the AV fistula is made or the PD training is given.Correspondence to:
Marta Duenhas, MD
Divisão de Nefrologia
Hospital do Servidor Público Estadual
Rua Pedro de Toledo, 1800 – CP 8570 04039-004, São Paulo, Brazil
Email: [email protected]
Original
Effectiveness of treatment with oral paricalcitol in patients on peritoneal dialysis: a Spanish multicenter study
Rosa Ramos, Miguel Pérez Fontán, Emilio Sánchez, Auxiliadora Bajo, Francesc Barbosa, Mercè Borràs and Teresa González
Page No. 394
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (394-401)
Effectiveness of treatment with oral paricalcitol in patients on peritoneal dialysis: a Spanish multicenter study
Rosa Ramos1, Miguel Pérez Fontán2, Emilio Sánchez3, Auxiliadora Bajo4, Francesc Barbosa5, Mercè Borràs6 and Teresa González7
1H. Vall d’Hebrón, Servicio de Nefrología, Barcelona, 2Complejo Hospitalario Universitario de A Coruña, Servicio de Nefrología, A Coruña, 3H. Universitario central de Asturias, Servicio de Nefrología, Oviedo, 4H. La Paz, Servicio de Nefrología, Madrid, 5H. del Mar, Servicio de Nefrología, Barcelona, 6H. Universitario Arnau de Vilanova, Servicio de Nefrología, Lleida, and 7H. Bellvitge, Servicio de Nefrología L’Hospitalet del Llobregat, Barcelona, Spain
Aims: Recently, oral form of paricalcitol has allowed extension of treatment to ambulatory patients on peritoneal dialysis but few data have been published about the benefits of paricalcitol in this subgroup. A multicenter, retrospective study was carried out to increase current knowledge on the effectiveness and safety of paricalcitol in 162 peritoneal dialyzed patients with secondary hyperparathyroidism. Methods: Case histories of patients treated with paricalcitol for at least 6 months were reviewed to extract data on 12 biochemical parameters related to bone disease and health status. Changes in these parameters were described. Doses of paricalcitol and other concomitant treatments were evaluated at least every 3 months. Results: 99 men (61.1%) and 63 women (38.9%) with an average age of 62.07 years were included. PTH levels showed an acute decrease in the three first months (35.88%) and a global decrease at month 6 of 42.39%. A slight increase in calcium was observed (p < 0.001) but it remained between normal range values. Only 5 patients presented serum calcium over 10.2 in two consecutive measurements. No changes were found in phosphorus, calcium-phosphorus product, hemoglobin, alkaline phosphatase, GGT, albumin, PCR inflammatory markers, pH and bicarbonate. The decrease in proteinuria levels was nearly statistically significant (p = 0.061). Only 6 patients (0.36%) abandoned the treatment. Conclusions: Paricalcitol therapy was well tolerated with a high effectiveness in patients on peritoneal dialysis. A slight increase in serum calcium levels was observed, although within normal ranges. No changes in other biochemical parameters related to bone disease could be associated to paricalcitol with data compiled in our study. Paricalcitol seems to have a protective effect on proteinuria levels.Correspondence to:
Rosa Ramos, Hospital Vall d’Hebrón. Passeig de la Vall d’Hebron 119-129, 08035. Servicio de Nefrología, Barcelona, Spain
Email: [email protected]
Nephrology Education
The first case report of peritoneal dialysis related peritonitis caused by Microbacterium paraoxydans
Masahito Miyamoto, Tsutomu Sakurada, Daisuke Oishi, Kenichiro Koitabashi, Ken Hanada, Hiroshi Takemura, Yugo Shibagaki, Takashi Yasuda and Kenjiro Kimura
Page No. 402
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (402-406)
The first case report of peritoneal dialysis related peritonitis caused by Microbacterium paraoxydans
Masahito Miyamoto1, Tsutomu Sakurada1, Daisuke Oishi1, Kenichiro Koitabashi1, Ken Hanada1, Hiroshi Takemura2, Yugo Shibagaki1, Takashi Yasuda1 and Kenjiro Kimura1
1Division of Nephrology and Hypertension, Department of Internal Medicine, and 2Department of Microbiology, St. Marianna University School of Medicine, Kawasaki, Japan
Peritonitis is still the major complication associated with peritoneal dialysis (PD). Microbacterium spp., a type of coryneform bacteria, is an environmental bacterium isolated from soil, waste water and animals. Human infection is rare, and only few cases have so far been reported in immunocompromised hosts, such as PD patients. Microbacterium paraoxydans, one type of Microbacterium spp. was identified for the first time in 2003. Only two cases of infection of Microbacterium paraoxydans have so far been reported. We herein report the first case of PD-related peritonitis caused by Microbacterium paraoxydans, which was identified by a sequence determination of the 16S rRNA gene. Based on the results of antibiotic sensitivity, the intravenous administration of erythromycin (EM) and oral administration of sulfamethoxazole/trimethoprim (ST) were selected, and PD was interrupted. EM administration was stopped after a total of 14 days. ST was administered for a total of 21 days, and later PD was resumed. Thereafter, no recurrence or relapse of peritonitis without removal of the PD catheter was observed. Microbacterium spp. exhibits multidrug resistance and such an infection is refractory in many cases. We assume that both accurate species identification and the use of antibiotic sensitivity tests are essential to effectively treat this kind of infection.Correspondence to:
Masahito Miyamoto, MD, PhD
Division of Nephrology and Hypertension
Department of Internal Medicine
St. Marianna University School of Medicine
2-16-1 Sugao, Miyamae-ku,
Kawasaki, Kanagawa 216-8511, Japan
Email: [email protected]
Nephrology Education
Successful interventional treatment of post-biopsy renal artery pseudoaneurysm in pediatric patients
Ru Xue, Mo Wang, Qiu Li, Xiao Dong Zhao, Xue Mei Tang, Ji Sheng Shi, Ling He, Qiao Wang, Shan Wang and Xiao Ping Luo
Page No. 407
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (407-413)
Successful interventional treatment of post-biopsy renal artery pseudoaneurysm in pediatric patients
Ru Xue1,2, Mo Wang2, Qiu Li2, Xiao Dong Zhao2, Xue Mei Tang2, Ji Sheng Shi2, Ling He3, Qiao Wang4, Shan Wang5 and Xiao Ping Luo6
1Laboratory of Clinical Immunology, Institute of Children Pediatric Research, 2Department of Nephroimmunology, 3Department of Radiology, 4Department of Ultrasonic Medicine, 5Department of Oncological Surgery, Children’s Hospital of Chongqing Medical University, and 6Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Background: With an incidence ranging from 0.01% to 1.0%, renal artery pseudoaneurysm (RAP) is a rare complication after renal biopsy, percutaneous renal surgery, penetrating trauma, and rarely blunt renal trauma. Methods: Percutaneous renal biopsy (PRB) of native kidneys was performed in 1,500 pediatric patients under real-time ultrasonographic guidance at our institution from July 1999 to January 2011. A retrospective review of these cases revealed that 2 patients developed a post-biopsy RAP. The diagnosis of RAP was established using color duplex ultrasonography (US), contrastenhanced computed tomography (CT) and digital substraction angiography (DSA). Results: Two patients developed RAP after 1,500 PRBs were performed (0.13% incidence). In the presented cases, immediate post-bioptic ultrasound showed no abnormalities. A high index of suspicion for RAP was prompted when complications such as unexplained gross hematuria and anemia occurred and the arterial phase of CT showed a well-circumscribed hyperdense area with a contrast enhancement similar to the adjacent arterial vessels. The diagnosis was confirmed by DSA and then the feeding artery of RAP was successfully occluded. After the procedure, the patients recovered and were discharged shortly. Conclusion: RAP is a rare, but potentially life-threatening complication after PRB and can be treated successfully with superselective arterial embolization.Correspondence to:
Mo Wang
Department of Nephroimmunology
Children’s Hospital of Chongqing
Medical University
136 Second Zhongshan Road
Yuzhong District, Chongqing 400014, China
Email: [email protected]
Nephrology Education
WT1 microdeletion and slowly progressing focal glomerulosclerosis in a patient with male pseudohermaphroditism, childhood leukemia, Wilms tumor and cerebellar angioblastoma
Gergely Buglyó, Gábor Méhes, György Vargha, Sándor Biró and János Mátyus
Page No. 414
Abstract
Clinical Nephrology, Vol. 79 – No. 5/2013 (414-418)
WT1 microdeletion and slowly progressing focal glomerulosclerosis in a patient with male pseudohermaphroditism, childhood leukemia, Wilms tumor and cerebellar angioblastoma
Gergely Buglyó1, Gábor Méhes2, György Vargha1, Sándor Biró1 and János Mátyus3
1Department of Human Genetics, 2Department of Pathology and 31st Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
The Wilms tumor 1 (WT1) gene is currently in focus by pediatric nephrologists as its mutations are associated with nephrotic syndrome, especially as part of complex clinical entities like Denys-Drash or Frasier syndrome. Renal failure may also develop in young WAGR patients, whose condition is attributed to a deletion at chromosomal region 11p13. However, only limited data exist on WT1 microdeletions. A 30-year-old male patient, with a history of genital malformations, a Wilms tumor manifested during the treatment of acute lymphoid leukemia (ALL) at the age of 4, and a cerebellar angioblastoma, was referred with proteinuria and a reduced glomerular filtration rate (GFR). Kidney biopsy revealed FSGS. Although all WT1 exons were amplified with polymerase chain reaction (PCR) and sequenced, none of them showed a mutation. However, an formalin-fixed, paraffin- embedded (FFPE) tissue sample of the patient’s childhood Wilms tumor showed WT1- positivity restricted to the renal tumor cells, so the WT1 gene was investigated further. Using quantitative reverse transcription PCR (qRT-PCR), the gene was found to be present in only one copy in the patient’s genomic DNA sample, while both copies were detected in both parents. In the patient’s sister, the proximal region of WT1 was shown to have an extra copy. Evidence suggests that a heterozygous microdeletion of the gene WT1 is responsible for the patient’s disease. It seems reasonable to assume a possible abnormality affecting meiotic crossing over at the WT1 locus in one of the parents.Correspondence to:
Sándor Biró, PhD
University of Debrecen
Department of Human Genetics
Nagyerdei krt. 98, Debrecen, 4032 Hungary
Email: [email protected]
Abstract
Book Review, Erratum
